This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The level of obesity has reached epidemic proportions [1] and contributes to increased mortality and morbidity [2]. Part of both mortality and morbidity arises from an increased incidence of insulin resistance and diabetes. However, it is possible to prevent progression to diabetes. A recent study has shown that when patients with insulin resistance were treated prior to the development of diabetes, there was a dramatic decrease in the number of subjects who went on to develop the disease [3]. Although several conventional drugs are effective in treating the insulin resistance associated with type 2 diabetes mellitus, the dietary supplement chromium picolinate has also been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus[4]. Intriguingly, chromium is comparatively inexpensive and apparently well-tolerated [4]. Specific Aim 1 of this proposal will examine the safety and efficacy of supplemental chromium picolinate in the treatment of insulin resistance in obesity-related insulin resistance. We will assess improvements in insulin sensitivity in a placebo-controlled study of chromium supplementation over a two-month course of therapy. We will also assess the safety of chromium picolinate treatment. Parameters of liver, renal function and oxidative damage will be monitored for possible chromium-related toxicities.